Recovery of Neurological Function after Traumatic Brain/Spinal CordInjury with Autologous Bone Marrow Stromal Cells

• Project/Area Number: 18390387
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Hokkaido University
• Principal Investigator: KURODA Satoshi Hokkaido University, 北海道大学病院, 講師 (10301904)
• Co-Investigator(Kenkyū-buntansha): IWASAKI Yoshinobu 北海道大学, 大学院・医学研究科, 教授 (00113522) ; HIDA Kazutoshi 北海道大学, 大学院・医学研究科, 准教授 (10238305) ; KOBAYASHI Hiroyuki 北海道大学, 病院, 助教 (70374478) ; YANO Shunsuke 北海道大学, 病院, 助教 (20374481) ; NAKAYAMA Naoki 北海道大学, 病院, 助教 (40421961)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,880,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥2,880,000); Fiscal Year 2008: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2007: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2006: ¥5,400,000 (Direct Cost: ¥5,400,000)
• Keywords: 神経再生 / 骨髄間質細胞 / 脊髄損傷 / 脳損傷 / Bone marrow stromal cell / Transplantation / Cerebral infarction / Spinal cord injury / Diffuse axonal iniury / Differentiation / Regenerative medicine / Functional restoration / Diffuse axonal injury / Diffuse brain injury / Cognitive function / DNA microarray

Research Abstract

この3年間に表記の研究課題に関して数多くの知見を得ることができた。すなわち、自己骨髄から分離した骨髄間質細胞(bone marrow stromal cells; BMSC)の生物学的特性を解明し、脳・脊髄内におけるBMSCの挙動を神経機能解析、DNAマイクロアレイ、免疫染色、光イメージング、MRIなどの手法を用いて多面的に解析した。この研究を通して、自己骨髄細胞を移植することによって、脳挫傷や脊髄損傷の患者さんの神経機能を回復させるための治療方法を開発する上で重要なステップを形成した。

Research Products

• [Journal Article] Transplanted bone marrow stromal cells promote axonal regeneration and improve motor function in rat spinal cord injury mode (2009)
  • Author(s): Chiba Y, Kuroda S, Maruichi K, Osanai T, Hokari M, Yano S, Shichinohe H, Hida K, Iwasaki Y
  • Journal Title: Neurosurgery 64 Pages: 991-1000
  • Peer Reviewed
• [Journal Article] Biodegradable fibrin scaffold enhances survival, migration and differentiation of transplanted bone marrow stromal cells in cortical freezing injury model of rats (2009)
  • Author(s): Yasuda H, Kuroda S, Shichinohe H, Kamei S, Kawamura R, Iwasaki Y
  • Journal Title: J Neurosurg (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Transplanted bone marrow stromal cells improves cognitive dysfunction due to diffuse axonal injury in rats (2009)
  • Author(s): Maruichi K, Kuroda S, Chiba Y, Hokari M, Shichinohe H, Hida K, Iwasaki Y
  • Journal Title: Neuropathology (e-pub)
  • NAID: 10028191635
• [Journal Article] Synergistic effects of granulocyte-colony stimulating factor on bone marrow stromal cell transplantation for mice cerebral infarct (2009)
  • Author(s): Hokari M, Kuroda S, Chiba Y, Maruichi K, Iwasaki Y
  • Journal Title: Cytokine(Epub ahead of print) 46 Pages: 260-266
  • Peer Reviewed
• [Journal Article] Graded model of diffuse axonal injury for studying head injury-induced cognitive dysfunction in rats (2009)
  • Author(s): Maruichi K, Kuroda S, Chiba Y, Hokari M, Shichinohe H, Hida K, Iwasaki Y
  • Journal Title: Neuropathology(e-pub) 29 Pages: 132-139
  • NAID: 10026608745
  • Peer Reviewed
• [Journal Article] Bone marrow stromal cell transplantation for cerebral infarction - recent advances and perspective (2009)
  • Author(s): Shichinohe H, Kuroda S
  • Journal Title: Res Adv in Stroke 1 Pages: 23-35
  • Peer Reviewed
• [Journal Article] Transplanteds bone marrow stromal cells improve cognitiye dysfunction due to diffuse axonal injury in rats (2009)
  • Author(s): Maruichi K, et.al.
  • Journal Title: Neuropathology (E-pub)
  • Peer Reviewed
• [Journal Article] Biodegradable fibrin scaffold enhances survival, migration, and differentiation of transplanted bone marrow (2009)
  • Author(s): Yasuda H, et.al.
  • Journal Title: J Neurosurg (E-pub)
  • Peer Reviewed
• [Journal Article] Transplanted bone marrow stromal cells promote axonal regeneration and improve motor function in rat (2009)
  • Author(s): Chiba Y, et.al.
  • Journal Title: Neurosurgery (In press)
  • Peer Reviewed
• [Journal Article] Synergistic effects of granulocyte-colony stimulating factor on bone marrow stromal cell transplantation (2009)
  • Author(s): Hokari M, et.al.
  • Journal Title: Cytokine (E-pub)
  • Peer Reviewed
• [Journal Article] Bone marrow stromal cell transplantation for cerebral infarction-recent advances and perspective (2009)
  • Author(s): Shichinohe H, et.al.
  • Journal Title: Res Adv in Stroke 1 Pages: 23-35
  • Peer Reviewed
• [Journal Article] 骨髄間質細胞を用いた損傷脊髄の再生 (2009)
  • Author(s): 千葉泰弘, ら
  • Journal Title: リハビリテーション医学 45 Pages: 356-360
• [Journal Article] 中枢神経再生におけるバイオマテリアルの役割 (2009)
  • Author(s): 長内俊也, ら
  • Journal Title: 再生医療 7 Pages: 77-82
  • Peer Reviewed
• [Journal Article] ラボから急性期脳梗塞治療ヘ-ラジカルスカベンジャーと骨髄間質細胞移植 (2009)
  • Author(s): 黒田敏
  • Journal Title: 脳卒中 30 Pages: 875-879
  • Peer Reviewed
• [Journal Article] Fibrin matrix provides a suitable scaffold for bone marrow stromal cells transplanted into injured spinal cord - A novel material for CNS tissue engineering (2008)
  • Author(s): Itosaka H, Kuroda S, Shichinohe H, Yasuda H, Yano S, Kamei S, Kawamura R, Hida K, Iwasaki Y
  • Journal Title: Neuropathology 20
  • NAID: 10026609224
  • Peer Reviewed
• [Journal Article] Edaravone (MCI-186) scavenges reactive oxygen species and ameliorates tissue damage in mice spinal cord injury model (2008)
  • Author(s): Aoyama T, Hida K, Kuroda S, Seki T, Yano S, Shichinohe H, Iwasaki Y
  • Journal Title: Neurol Med Chir 48 Pages: 539-545
  • Peer Reviewed
• [Journal Article] Bone marrow stromal cells differentiate into neurons and promote axon elongation in spinal cord slice cultures : Their role in cell transplantation therapy for spinal cord injury (2008)
  • Author(s): Shichinohe H, Kuroda S, Tsuji S, Yamaguchi S, Yano S, Lee JB, Kobayashi H, Hokari M, Hida K, Kikuchi S, Iwasaki Y
  • Journal Title: Neurorehabil Neural Repair 22 Pages: 447-457
  • Peer Reviewed
• [Journal Article] Bone marrow stromal cells protect and repair damaged neurons through multiple mechanisms (2008)
  • Author(s): Hokari M, Kuroda S, Shichinohe H, Yano S, Hida K, Iwasaki Y
  • Journal Title: J Neurosci Res 86 Pages: 1024-1035
  • Peer Reviewed
• [Journal Article] 骨髄間質細胞を用いた損傷脊髄の再生 (2008)
  • Author(s): 千葉泰弘、黒田 敏、穂刈正昭、矢野俊介、飛騨一利、岩崎喜信
  • Journal Title: リハビリテーション医学 45 Pages: 356-360
  • NAID: 110006792789
• [Journal Article] 中枢神経再生におけるバイオマテリアルの役割 (2008)
  • Author(s): 長内俊也、黒田 敏、岩崎喜信
  • Journal Title: 再生医療 7 Pages: 77-82
  • NAID: 40016387509
  • Peer Reviewed
• [Journal Article] ラボから急性期脳梗塞の治療へーラジカルスカベンジャーと骨髄細胞移植 (2008)
  • Author(s): 黒田 敏
  • Journal Title: 脳卒中 30 Pages: 875-879
  • NAID: 10024937358
• [Journal Article] Bone marrow stromal cells protect and repair damaged neurons through multiple mechanisms (2008)
  • Author(s): Hokari M, et.al.
  • Journal Title: J Neurosci Res 86 Pages: 1024-1035
  • Peer Reviewed
• [Journal Article] Graded model of diffuse axonal injury for studying head Injury-induced cognitive dysfunction in rats (2008)
  • Author(s): Maruichi K, et.al.
  • Journal Title: Neuropathology (E-pub)
  • Peer Reviewed
• [Journal Article] Bone marrow stromal cells differentiate into neurons And promote axon elongation in spinal cord slice (2008)
  • Author(s): Shichinohe H, et.al.
  • Journal Title: Neurorehabil Neural Repair 22 Pages: 447-457
  • Peer Reviewed
• [Journal Article] Fibrin matrix provides a suitable scaffold for bone marrow stromal cells transplanted into (2008)
  • Author(s): Itosaka H, et.al.
  • Journal Title: Neuropathology (E-pub)
  • Peer Reviewed
• [Journal Article] Edaravone (MCI186) scavenges reactive oxygen species and ameliorates tissue damage in mice spinal cord (2008)
  • Author(s): Aoyama T, et.al.
  • Journal Title: Neurol Med Chir (Tokyo) 48 Pages: 539-545
  • Peer Reviewed
• [Journal Article] Bone marrow stromal cells protect and repair damaged neurons… (2008)
  • Author(s): Hokari, et. al.
  • Journal Title: J Neurosci Res 86 Pages: 1024-1035
  • Peer Reviewed
• [Journal Article] Role of SDF-1/CXCR4 system in survival and migration of bone marrow stromal cells after transplantation into mice cerebral infarct (2007)
  • Author(s): Shichinohe H, Kuroda S, Yano S, Hida K, Iwasaki Y
  • Journal Title: Brain Res 1183 Pages: 138-147
  • Peer Reviewed
• [Journal Article] 骨髄間質細胞を用いた脊髄損傷の再生 (2007)
  • Author(s): 黒田 敏、穂刈正昭、千葉泰弘、七戸秀夫、矢野俊介、飛騨一利、岩崎喜信
  • Journal Title: 脊椎脊髄ジャーナル 20 Pages: 1233-1237
• [Journal Article] 脳損傷の病態と高次脳機能障害-再生治療の展望- (2007)
  • Author(s): 丸一勝彦、黒田 敏、岩崎喜信
  • Journal Title: 脳外 35 Pages: 965-969
  • Peer Reviewed
• [Journal Article] Role of SDF-1/CXCR4 system in survival and migration of… (2007)
  • Author(s): Shichinohe, et. al.
  • Journal Title: Brain Res 1183 Pages: 138-147
  • Peer Reviewed
• [Journal Article] 脳SPECT/PETによる選択的神経細胞障害のイメージング (2007)
  • Author(s): 黒田 敏
  • Journal Title: 分子脳血管病 6 Pages: 293-299
• [Journal Article] 骨髄間質細胞を用いた脊髄損傷の再生 (2007)
  • Author(s): 黒田 敏
  • Journal Title: 脊椎脊髄ジャーナル 20 Pages: 1233-1237
• [Journal Article] 脳損傷の病態と高次脳機能障害-再生治療の展望- (2007)
  • Author(s): 丸一勝彦
  • Journal Title: 脳外 35 Pages: 965-969
  • Peer Reviewed
• [Journal Article] Improved expression of gamma-aminobutyric acid receptor in mice with cerebral infarct and transplanted bone marrow stromal cells (2006)
  • Author(s): Shichinohe H, Kuroda S, Yano S, Ohnishi T, Tamagami H, Hida K, Iwasaki Y
  • Journal Title: An autoradiographic and histologic analysis 47 Pages: 486-491
  • Peer Reviewed
• [Journal Article] The effects of neuronal induction on gene expression profile in bone marrow stromal cells (BMSC) - a preliminary study using microarray analysis (2006)
  • Author(s): Yamaguchi S, Kuroda S, Kobayashi H, Shichinohe H, Yano S, Hida K, Shinpo K, Kikuchi S, Iwasaki Y
  • Journal Title: Brain Res 1087 Pages: 15-27
  • Peer Reviewed
• [Journal Article] Bone marrow stromal cell transplantation preserves gamma-aminobutyric acid (GABA) receptor function in injured spinal cord (2006)
  • Author(s): Yano S, Kuroda S, Shichinohe H, Lee JB, Ohnishi T, Tamagami H, Hida K, Iwasaki Y
  • Journal Title: J Neurotrauma 23 Pages: 1682-1692
  • Peer Reviewed
• [Journal Article] 骨髄間質細胞を用いた脊髄損傷の再生は" Mission Impossible"か? (2006)
  • Author(s): 黒田 敏、岩崎喜信
  • Journal Title: 分子脳血管病 5 Pages: 436-442
• [Journal Article] Improved expression of gamma-aminobutyric acid receptor in mice with cerebral infarct and transplanted bone marrow stromal cells (2006)
  • Author(s): Shichinohe H, Kuroda S, et al.
  • Journal Title: J Nucl Med 47 Pages: 486-491
• [Journal Article] The effects of neuronal induction on gene expression profile in bone marrow stromal cells (BMSC) (2006)
  • Author(s): Yamaguchi S, Kuroda S, et al.
  • Journal Title: Brain Res 1087 Pages: 15-27
• [Journal Article] Susceptibility of brain microvascular endothelial cells to advanced glycation end products-induced tissue factor upregulation (2006)
  • Author(s): Niiya Y, Kuroda S, et al.
  • Journal Title: Brain Res 1108 Pages: 179-187
• [Journal Article] Bone marrow stromal cell transplantation preserves gamma-aminobutyric acid (GABA) receptor function in injured spinal cord (2006)
  • Author(s): Yano S, Kuroda S, et al.
  • Journal Title: J Neurotrauma 23 Pages: 1682-1692
• [Journal Article] Cerebral oxygen metabolism and neuronal integrity in patients with impaired vasoreactivity due to occlusive carotid artery diseases (2006)
  • Author(s): Kuroda, et al.
  • Journal Title: Stroke 37 Pages: 393-398
• [Journal Article] Clinical features of familial moyamoya disease (2006)
  • Author(s): Nanba R, Kuroda S, et al.
  • Journal Title: Child Nerv Syst 22 Pages: 258-262
• [Journal Article] Bone marrow stromal cells differentiate into neurons and promote…
  • Author(s): Shichinohe, et. al.
  • Journal Title: Neurorehabil Neural Repair (in press)
  • Peer Reviewed
• [Journal Article] 骨髄間質細胞を用いた損傷脊髄の再生
  • Author(s): 千葉泰弘
  • Journal Title: リハビリテーション医学 (in press)
• [Presentation] 脳卒中に対する骨髄間質細胞移植研究の現状と課題 (2009)
  • Author(s): 黒田 敏ら
  • Organizer: 日本脳卒中学会
  • Place of Presentation: 松江
• [Presentation] Bone marrow stromal cell transplantation for central nervous system disorders (2009)
  • Author(s): Kuroda S, et.al.
  • Organizer: International Symposium for Future Drug Discovery and Medical Care
  • Place of Presentation: Sapporo
• [Presentation] 塩酸ファスジルは脊髄損傷に対する骨髄間質細胞の移植効果を増強するか? (2009)
  • Author(s): 千葉泰弘ら
  • Organizer: 日本再生医療学会
  • Place of Presentation: 東京
• [Presentation] 骨髄間質細胞移植のバイオマテリアルとしてのMebiol gelの有用性について (2009)
  • Author(s): 長内俊也ら
  • Organizer: 日本再生医療学会
  • Place of Presentation: 東京
• [Presentation] 骨髄間質細胞の移植はびまん性軸策損傷による高次脳機能障害を改善する (2009)
  • Author(s): 丸一勝彦ら
  • Organizer: 日本再生医療学会
  • Place of Presentation: 東京
• [Presentation] 長波長蛍光物質で標識した骨髄間質細胞の頭蓋内光イメージング (2009)
  • Author(s): 杉山 拓ら
  • Organizer: 日本再生医療学会
  • Place of Presentation: 東京
• [Presentation] 塩酸ファスジルは脊髄損傷に対する骨髄間質細胞の移植効果を増強するか (2009)
  • Author(s): 千葉泰弘, ら
  • Organizer: 日本再生医療学会
  • Place of Presentation: 東京
• [Presentation] 骨髄間質細胞の移植はびまん性脳損傷による高次脳機能障害を改善する (2008)
  • Author(s): 丸一勝彦ら
  • Organizer: 日本再生治療学会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-03-13
• [Presentation] 骨髄間質細胞の移植は損傷脊髄における皮質脊髄路の再生を促進する (2008)
  • Author(s): 千葉泰弘ら
  • Organizer: 日本再生治療学会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-03-13
• [Presentation] 顆粒球コロニー刺激因子は骨髄間質細胞の移植効果を賦活する (2008)
  • Author(s): 穂刈正昭ら
  • Organizer: 日本再生治療学会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-03-13
• [Presentation] 自己骨髄細胞による損傷脊髄の再生 (2008)
  • Author(s): 黒田 敏ら
  • Organizer: 日本脊髄障害医学会総会
  • Place of Presentation: 札幌
• [Presentation] Mitochondrial trans- cription factor Aは虚血による神経細胞障害を軽減する (2008)
  • Author(s): 穂刈正昭ら
  • Organizer: 日本脳循環代謝学会
  • Place of Presentation: 東京
• [Presentation] Transplanted bone marrow stromal cells improve cognitive dysfunction due to diffuse axonal injury in rats (2008)
  • Author(s): Maruichi K, et.al.
  • Organizer: American Association of Neurological Surgeons
  • Place of Presentation: Chicago
• [Presentation] Transplanted bone marrow stromal cells promote axonal regeneration and improve motor function in rat spinal cord injury (2008)
  • Author(s): Chiba Y, et al.
  • Organizer: American Association of Neurological Surgeons
  • Place of Presentation: Chicago
• [Presentation] ラボから急性期脳梗塞の治療へ : ラジカルスカベンジャーと骨髄細胞移植 (2008)
  • Author(s): 黒田 敏ら
  • Organizer: 日本脳卒中学会
  • Place of Presentation: 京都
• [Presentation] Transplanted bone marrow stromal cells promote axonal regeneration and improve motor function in rat (2008)
  • Author(s): Chiba Y, et.al.
  • Organizer: American Association of Neurological Surgeons
  • Place of Presentation: Chicago
• [Presentation] Mitochondrial transcription factor Aは虚血による神経細胞障害を軽減する (2008)
  • Author(s): 穂刈正昭, ら
  • Organizer: 日本脳循環代謝学会
  • Place of Presentation: 東京
• [Presentation] 骨髄間質細胞を用いた損傷脊髄の再生 (2007)
  • Author(s): 黒田 敏ら
  • Organizer: 日本リハビリテーション医学会
  • Place of Presentation: 神戸
  • Year and Date: 2007-06-06
• [Presentation] 障害された神経細胞に対する骨髄間質細胞の神経保護効果-修復メカニズムの解明 (2007)
  • Author(s): 穂刈正昭ら
  • Organizer: 日本脳卒中学会
  • Place of Presentation: 福岡
• [Presentation] 移植された骨髄間質細胞の増殖・遊走におけるSDF-1/CXCR4系の役割について (2006)
  • Author(s): 七戸秀夫ら
  • Organizer: 日本脳神経外科学会
  • Place of Presentation: 京都
• [Book] 骨髄間質細胞移植による中枢神経再生-最近の進歩。Annual Review 神経2007 (2007)
  • Author(s): 黒田敏, 岩崎喜信
  • Publisher: 中外医学社
• [Book] Annual Review神経 (2007)
  • Author(s): 黒田 敏
  • Total Pages: 450
  • Publisher: 骨髄間質細胞による中枢神経再生-最近の進歩
• [Book] Annual Review神経2007 (2007)
  • Author(s): 黒田 敏, 岩崎喜信
  • Total Pages: 500
  • Publisher: 中外医学社
• [Book] Transplanted bone marrow stromal cells improves cognitive dysfunction due to diffuse axonal injury in rats
  • Author(s): Maruichi K, Kuroda S, Chiba Y, Osanai T, Sugiyama T, Hokari M, Hida K, Iwasaki Y
  • Publisher: Kuge Y (ed) Molecular Imaging for Integrated Medical Therapy and Drug Development (in press)
• [Book] Non-invasive optical tracking of bone marrow stromal cells transplanted into rat cerebral infarct
  • Author(s): Sugiyama T, Kuroda S, Osanai T, Maruichi K, Chiba Y, Shichinohe H, Kuge Y, Tamaki N, Iwasaki Y
  • Publisher: Kuge Y (ed) Molecular Imaging for Integrated Medical Therapy and Drug Development (in press)
• [Book] Beneficial effects of bone marrow stromal cell transplantation on axonal regeneration in injured spinal cord
  • Author(s): Chiba Y, Kuroda S, Maruichi K, Osanai T, Hokari M, Yano S, Shichinohe H, Hida K, Iwasaki Y
  • Publisher: Kuge Y (ed) Molecular Imaging for Integrated Medical Therapy and Drug Development (in press)
• [Book] Thermoreversible gelation polymer (TGP) hydrogel as a degradable scaffold for bone marrow stromal cell transplantation
  • Author(s): Osanai T, Kuroda S, Yasuda H, Chiba Y, Maruichi K, Hokari M, Sugiyama T, Shichinohe H, Iwasaki Y
  • Publisher: Kuge Y (ed) Molecular Imaging for Integrated Medical Therapy and Drug Development (in press)
• [Book] Bone marrow stromal cell transplantation for central nervous system disorders - Perspective for translational research and clinical application
  • Author(s): Kuroda S, Kuge Y, Tamaki N, Iwasaki Y
  • Publisher: Kuge Y (ed) Molecular Imaging for Integrated Medical Therapy and Drug Development (in press)